Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

Department of Biomedical Science, Cummings School of Veterinary Medicine, Tufts University North Grafton, MA, USA.
Frontiers in Psychiatry 01/2011; 2:29. DOI: 10.3389/fpsyt.2011.00029
Source: PubMed

ABSTRACT The non-medical use of prescription opiates, such as Vicodin(®) and MSContin(®), has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females' spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

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    ABSTRACT: Prescription opiate use by adolescent girls has increased significantly in the past decade. Preclinical studies using rats report alterations in morphine sensitivity in the adult offspring of adolescent morphine-exposed females (MOR-F1) when compared with the offspring of adolescent saline-exposed females (SAL-F1). To begin to elucidate the development of these next generation modifications, the present study examined the effects of acute morphine administration on sedation and corticosterone secretion in prepubescent SAL-F1 and MOR-F1 male and female rats. In addition, alterations in proopiomelanocortin (POMC) gene expression in the arcuate nucleus, as well as in tyrosine hydroxylase (TH) and μ-opioid receptor (OPRM1) gene expressions in the ventral tegmental area, were analyzed using quantitative PCR, to determine whether differential regulation of these genes was correlated with the observed behavioral and/or endocrine effects. Increased morphine-induced sedation, coupled with an attenuation of morphine-induced corticosterone secretion, was observed in MOR-F1 males. Significant alterations in both POMC and OPRM1 gene expressions were also observed in MOR-F1 males, with no change in TH mRNA expression. Overall, these data suggest that the transgenerational effects of adolescent morphine exposure can be discerned before pubertal development and are more pronounced in males, and suggest dysregulation of the hypothalamic-pituitary-adrenal axis in the offspring of adolescent morphine-exposed females.
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